PB2450: SEX-ASSOCIATED OUTCOME DIFFERENCES IN PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) UNDERGOING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT)
Authors: Jule Ussmann, Lara Bischof, Donata Backhaus, Dominic Brauer, Rosmarie Pointner, Georg-Nikolaus Franke, Vladan Vucinic, Maximilian Merz, Uwe Platzbecker, Sebastian Schwind, Madlen Jentzsch
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Recent identifications of sex-associated differences in the biology of hematologic neoplasm highlights the need to explore sex as a so far underestimated factor influencing outcomes. In unselected hematologic neoplasm, female sex had a beneficial impact on overall survival (OS) after HSCT. While HSCT remains the only curative treatment for high-risk AML patients (pts), data on sex-associated outcome differences in AML after HSCT remain sparse. Aims: To compare outcomes and risk factors of female and male AML pts undergoing HSCT at our center. Methods: We retrospectively analyzed 451 AML pts (216 female, 235 male) who underwent HSCT (median age 63, range 27-77 years) in first (78%) or second (22%) complete remission with or without blood count recovery. Conditioning was non-myeloablative (nma, 86%), or reduced intensity (ric, 14%) and donors were matched sibling (MSD, 15%), matched unrelated (MUD, 61%), mismatch unrelated (MMUD, 23%), or haploidentical (2%). At AML diagnosis, pts were grouped according to the European LeukemiaNet (ELN) 2022 risk. Up to 28 days prior to HSCT, NPM1 or RUNX1-based measurable residual disease (MRD) was analyzed in mutated pts (20%) using digital droplet PCR. Results: At diagnosis, female pts had higher blood (P=.004) and bone marrow (P=.008) blast counts, more de novo AML (P=.03), and less often harbored spliceosome mutations (i.e., SRSF2, U2AF1, ZRSR2; P=.02) than male pts, while ELN2022 risk at diagnosis (P=.40) and the MRD status prior to HSCT (P=.39) did not differ between female and male pts. After HSCT, female pts showed significantly shorter time to leukocyte regeneration (P=.03) and a higher incidence of chronic Graft-versus-Host-Disease (cGvHD, P=.02). MSD (P>.99) and MMUD (P=.26) were equally allocated between sexes. Regarding outcomes, female pts had similar non relapse mortality (NRM, P=.96) but significantly lower cumulative incidence of relapse (CIR, P=.05; Figure 1A), and longer overall survival (OS, P=.02; Figure 1B) than male pts. Important AML-associated risk factors as the ELN2022 at diagnosis (CIR P=.02 and P=.10; OS P=.04 and P=.03) and the MRD status at HSCT (CIR P<.001 and P<.001; OS P=.03 and P=.01) impacted outcomes in both, female and male pts, respectively. Analyzing the impact of HSCT-related variables, male pts transplanted from an MSD had a higher CIR compared to MUD/MMUD (P=.005) but lower NRM (P=.02), resulting in a trend for shorter OS (P=.10) for MSD, while CIR (P=.21), NRM (P=.53), and OS (P=.50) did not differ according to the used donor in female pts. The development of acute GvHD ≥ grade II associated with significantly higher NRM and shorter OS in female (P=.02 and P=.01, respectively) and male pts (P<.001 and P<.001, respectively, Figure 1C). In contrast, the development of cGvHD associated with lower CIR in female (P=.005) and male (P<.001) pts, but also a trend for higher NRM in female pts (P=.08), resulting in similar OS in female (P=.80), but improved OS in male (P<.001) pts developing a cGvHD. Interestingly, only male pts who developed cGvHD obtained OS comparable to those of female pts after HSCT (Figure 1D). Summary/Conclusion: We observed distinct AML characteristics as well as lower CIR and longer OS after HSCT in female compared to male pts. Female pts had higher cGvHD rates, but only in male pts, development of cGvHD significantly improved OS. Together with the higher CIR in male pts transplanted from MSD, this data implies an increased need of a Graft-versus Leukemia effect in male, compared to female pts after nma or ric HSCT.Keywords: Gender, AML, Allogeneic hematopoietic stem cell transplant, Clinical outcome